Abstract
The posttranslational modification of clock proteins is critical for the function of circadian oscillators. By genetic analysis of a Drosophila melanogaster circadian clock mutant known as Andante, which has abnormally long circadian periods, we show that casein kinase 2 (CK2) has a role in determining period length. Andante is a mutation of the gene encoding the β subunit of CK2 and is predicted to perturb CK2β subunit dimerization. It is associated with reduced β subunit levels, indicative of a defect in α:β association and production of the tetrameric α2:β2 holoenzyme. Consistent with a direct action on the clock mechanism, we show that CK2β is localized within clock neurons and that the clock proteins Period (Per) and Timeless (Tim) accumulate to abnormally high levels in the Andante mutant. Furthermore, the nuclear translocation of Per and Tim is delayed in Andante, and this defect accounts for the long-period phenotype of the mutant. These results suggest a function for CK2-dependent phosphorylation in the molecular oscillator.
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Acknowledgements
We thank A. Schroeder and M. Roberts for help and advice, R. McConnell and the Tufts Integrated Confocal Facility for imaging services, M. Berne and the Tufts Molecular Core for DNA sequencing services, the Bloomington Stock Center for fly stocks and H. Dircksen (Universität Bonn) and R. Rao (University of West Florida) for anti-PDF antibody. We are grateful to R. Allada for communicating data on the circadian function of Drosophila CK2α prior to publication. This work was supported by the National Institutes of Health (F.R.J. and I.E.) and the Deutsche Forschungsgemeinschaft (T.R.).
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Akten, B., Jauch, E., Genova, G. et al. A role for CK2 in the Drosophila circadian oscillator. Nat Neurosci 6, 251–257 (2003). https://doi.org/10.1038/nn1007
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DOI: https://doi.org/10.1038/nn1007
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